omega-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Ca(v)2.2 Ion Channels

Tranberg, Charlotte Elisabet, Yang, Aijun, Vetter, Irina, McArthur, Jeffrey R., Baell, Jonathan B., Lewis, Richard J., Tuck, Kellie L. and Duggan, Peter J. (2012) omega-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Ca(v)2.2 Ion Channels. Marine Drugs, 10 10: 2349-2368. doi:10.3390/md10102349

Author Tranberg, Charlotte Elisabet
Yang, Aijun
Vetter, Irina
McArthur, Jeffrey R.
Baell, Jonathan B.
Lewis, Richard J.
Tuck, Kellie L.
Duggan, Peter J.
Title omega-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Ca(v)2.2 Ion Channels
Formatted title
ω-Conotoxin GVIA mimetics that bind and inhibit neuronal Ca v2.2 ion channels
Journal name Marine Drugs   Check publisher's open access policy
ISSN 1660-3397
Publication date 2012-10
Sub-type Article (original research)
DOI 10.3390/md10102349
Open Access Status DOI
Volume 10
Issue 10
Start page 2349
End page 2368
Total pages 20
Place of publication Basel, Switzerland
Publisher M D P I AG
Collection year 2013
Language eng
Formatted abstract
The neuronal voltage-gated N-type calcium channel (Ca v2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived ω-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a 125I-ω-conotoxin GVIA displacement assay, a fluorescence-based calcium response assay with SH-SY5Y neuroblastoma cells, and a whole-cell patch clamp electrophysiology assay with HEK293 cells stably expressing human Ca v2.2 channels. A subset of compounds were active in all three assays. This is the first time that compounds designed to be mimics of ω-conotoxin GVIA and found to be active in the 125I-ω- conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner.
Keyword Ca(v)2.2
radioligand binding
Ca2+ fluorescence assay
Patch clamp electrophysiology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
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